Beruflich Dokumente
Kultur Dokumente
Edward F. Goljan
Chapter 1, 1-7
Copyright 2014 by Saunders, an imprint of Elsevier Inc.
Chapter 1
Diagnostic Testing
I
Purpose of Laboratory Tests
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A.
Screen for disease
1.
General criteria for screening
a.
Effective therapy that is safe and inexpensive must be available.
b.
Disease must have a high enough prevalence to justify the expense.
c.
Disease should be detectable before symptoms surface in the patient.
d.
Test must not have many false positives (people misclassified as having disease).
e.
Test must have extremely high sensitivity.
Criteria for screening test: !sensitivity and prevalence; cost-effective; treatable
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2.
Examples of screening tests
a.
Newborn screening for inborn errors of metabolism
Definitionnumber of people with a specific disease who have a positive test result
2.
False negative (FN)
Definitionnumber of people with a specific disease who have a negative test result
Test results in people with disease: TP and FN
B.
Terms for test results for people without disease (see Fig. 1-1 )
1.
True negative (TN)
Control group should include people of various ages and both sexes, and those who have
diseases that are closely related to the disease for which the test is intended.
2.
Definitionlikelihood that a person without disease will have a negative test result
3.
Formula for calculating specificity is TN (TN + FP).
For example, if the serum antinuclear antibody (ANA) test returns negative on more than one
occasion, the diagnosis of SLE can be excluded.
Usefulness of test with 100% sensitivity: exclude disease when test returns normal
2.
When a test with 100% sensitivity returns positive on a patient, a test with 100% specificity (or close to it)
should be used to decide if the test result was a TP or a FP.
Usefulness of test with 100% specificity: distinguish TP from FP test result
a.
For example if the serum ANA returns positive in a patient who is suspected of having SLE, the
serum anti-Smith (Sm) and antidouble-stranded DNA test should be used because they both
have extremely high specificity for diagnosing SLE.
b.
If either or both tests return positive, the patient has SLE.
c.
If both tests consistently return negative, the patient most likely does not have SLE but some other
closely related disease.
III
Predictive Value of Positive and Negative Test Results
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A.
Predictive value of a negative test result (PV!)
1.
Definitionlikelihood that a negative test result is a TN rather than a FN
2.
Formula for calculating PV" is TN (TN + FN).
Disease is confirmed.
Specificity 100% # PV+ 100% # confirms disease
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C.
Effect of prevalence on PV! and PV+
1.
Definitiontotal number of people with disease in the population under study
Prevalence: total # people with disease in a population
Note that there is an overlap between the normal and the disease population in parts B and C of
Figure 1-4.
B.
Establishing a test with 100% sensitivity and PV! (see Fig. 1-4B )
1.
To establish a test with 100% sensitivity and PV !, set the cutoff point for the reference interval at the
beginning of the disease curve (A).
a.
Note that this creates a test with 100% sensitivity and 100% PV !, because there are no FNs
within the newly established reference interval (0 to A).
b.
Test can now be used to screen for disease.
!Sensitivity/PV !: put cutoff point at the beginning of the disease curve; no FNs
2.
Note that by increasing sensitivity there is always a corresponding decrease in the specificity and PV+
due to a greater number of FPs.
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C.
Establishing a test with 100% specificity and PV+ (see Fig. 1-4C )
1.
To establish a test with 100% specificity/PV+, set the upper cutoff point for the reference interval at the
end of the normal curve (B).
a.
Note that this creates a test with 100% specificity and 100% PV+, because there are no FPs
outside the reference interval (0 to B).
b.
Test can now be used to confirm disease.
!Specificity/PV+: put cutoff point at the end of the normal curve; no FPs
2.
Note that by increasing specificity there is always a corresponding decrease in sensitivity and PV !, due
to a greater number of FNs.
V
Variables Affecting Laboratory Test Results
A.
Premature newborns
1.
Variable hemoglobin (Hb) concentration depending on the gestational age
2.
Anemia in prematurity is due to:
a.
Iron deficiency, related to loss of the daily supply of iron from the mother's iron stores
b.
Blood loss from excessive venipunctures in the premature newborn
Anemia prematurity: loss of iron from mother; blood loss from venipuncture
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B.
Newborns
1.
Newborns have higher normal ranges for Hb, Hct, and RBC counts than do infants and children.
2.
HbF (2%/2& globin chains) shifts the OBC to the left causing the release of EPO.
For example, blood group A newborns lack anti-B IgM isohemagglutinin in their plasma.
Clinical correlation: Newborns with an increase in cord blood IgM may have an underlying congenital infection
(e.g., cytomegalovirus, rubella). Their blood should be screened for antibodies against the common congenital
infections.
Newborns: lack IgM at birth; !cord blood IgM indicates congenital infection
6.
IgG antibodies in newborns are of maternal origin.
a.
Newborns begin synthesizing IgG 2-3 months after birth.
b.
Adult levels of IgG are achieved by age 6 to 10 years.
Clinical correlation: A mother with a positive test for human immunodeficiency virus (e.g., IgG antibodies against
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the glyco protein gp120) transplacentally transfers IgG antibodies to the fetus. This does not mean that the child
is infected by the virus.
Newborns normally synthesize both IgM and IgG after birth
C.
Children
1.
When compared to an adult, children have higher serum alkaline phosphatase (ALP) levels.
a.
This is due to increased bone growth in children and release of ALP from osteoblasts.
b.
ALP removes the phosphate from pyrophosphate, which normally inhibits bone mineralization.
2.
When compared to an adult, children have higher serum phosphorus levels.
For normal mineralization of bone to occur, phosphorus is required to drive calcium into bone;
hence, the higher phosphorus levels in children.
3.
When compared to an adult, children have a lower Hb concentration (11.5 g/dL; anemia <11.5 g/dL).
a.
This is most likely related to the increased serum phosphorus levels in children.
Testosterone stimulates erythropoiesis, which also contributes to the higher Hb level in men
(13.5 g/dL; anemia <13.5 g/dL) than in women.
Women: $Hb, iron, ferritin than men
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2.
Advanced age
a.
Decrease in the glomerular filtration rate (GFR) and creatinine clearance (CCr)
For example, a purified protein derivative test for tuberculosis is weakly reactive in elderly
patients who have previously been exposed to tuberculosis.
Elderly: decrease in antibody synthesis and cellular immunity
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E.
Pregnancy
1.
Normal decrease in Hb concentration
a.
Due to an increase in plasma volume (PV) and RBC production (RBC mass) with a much greater
increase in PV than in RBC mass
Dilutional effect decreases the Hb concentration (normal 11 g/dL; anemia <11 g/dL).
Pregnancy: !!plasma volume, !RBC mass; !GFR, CCr
b.
Other effects of an increase in PV include:
(1)
Increased GFR and CCr
(2)
Increased renal clearance of blood urea nitrogen, creatinine, and uric acid with
corresponding lower levels in serum
2.
Increase in serum ALP (placental origin)
Pregnancy: !serum ALP (placental origin)
3.
Increase in serum human placental lactogen (HPL)
a.
Normally synthesized by syncytiotrophoblasts lining the chorionic villi in the placenta
b.
Inhibits the sensitivity of peripheral tissue to insulin
Excess acetyl CoA is produced, leading to increased liver synthesis of ketone bodies and
the normal ketonemia in pregnancy.
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4.
Mild respiratory alkalosis
a.
Due to stimulation of the respiratory center by estrogen and progesterone
b.
Increased pulmonary clearance of CO
2
is responsible for the respiratory alkalosis and is not
accompanied by an increase in respiratory rate.
Pregnancy: respiratory alkalosis due to estrogen/progesterone
c.
Decreased P CO
2
causes a corresponding increase in P O
2
in maternal blood, which increases
the amount of oxygen that is available to the developing fetus.
Arterial P O
2
is usually >100 mm Hg in pregnancy.
5.
Increase in the total serum thyroxine (T
4
) and cortisol (refer to Chapter 23)
a.
Normal measurement of total serum T
4
and cortisol includes bound and free fractions.
b.
Estrogen increases liver synthesis of the binding proteins for T
4
(thyroid binding globulin) and
cortisol (transcortin); however, the free hormone levels (metabolically active) are unaffected.
Because the free hormone levels are normal, the serum thyroid-stimulating hormone (TSH)
and adrenocorticotropic hormone (ACTH) are also normal.
Pregnancy: !total serum T
4
/cortisol; free hormone levels are normal
F.
Hemolyzed blood specimen related to venipuncture
1.
Potassium is the major intracellular cation; therefore a hemolyzed blood sample falsely increases serum
potassium (FP).
2.
RBCs primarily use anaerobic glycolysis as a source of ATP; therefore lactate dehydrogenase (LDH),
which normally converts pyruvate to lactate, is also falsely increased (FP).
Hemolyzed specimen: !serum K
+
, LDH
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